Shafiei Scott S, Guerrero-Muñoz Marcos J, Castillo-Carranza Diana L
Department of Neurology, Neuroscience and Cell Biology, University of Texas Medical BranchGalveston, TX, USA.
Department of Chemical Engineering, Hampton UniversityHampton, VA, USA.
Front Aging Neurosci. 2017 Apr 4;9:83. doi: 10.3389/fnagi.2017.00083. eCollection 2017.
Aging has long been considered as the main risk factor for several neurodegenerative disorders including a large group of diseases known as tauopathies. Even though neurofibrillary tangles (NFTs) have been examined as the main histopathological hallmark, they do not seem to play a role as the toxic entities leading to disease. Recent studies suggest that an intermediate form of tau, prior to NFT formation, the tau oligomer, is the true toxic species. However, the mechanisms by which tau oligomers trigger neurodegeneration remain unknown. This review summarizes recent findings regarding the role of tau oligomers in disease, including release from cells, propagation from affected to unaffected brain regions, uptake into cells, and toxicity via mitochondrial dysfunction. A greater understanding of tauopathies may lead to future advancements in regards to prevention and treatment.
长期以来，衰老一直被视为包括一大类被称为tau蛋白病的疾病在内的几种神经退行性疾病的主要风险因素。尽管神经原纤维缠结（NFTs）已被视为主要的组织病理学标志，但它们似乎并不是导致疾病的毒性实体。最近的研究表明，在NFT形成之前，tau蛋白的一种中间形式，即tau寡聚体，才是真正的毒性物质。然而，tau寡聚体引发神经退行性变的机制仍不清楚。这篇综述总结了关于tau寡聚体在疾病中的作用的最新发现，包括从细胞中释放、从受影响的脑区传播到未受影响的脑区、被细胞摄取以及通过线粒体功能障碍产生毒性。对tau蛋白病的更深入了解可能会在预防和治疗方面带来未来的进展。
